Multiple sclerosis (MS) is a chronic inflammatory disease of the white and grey matter of the central nervous system (CNS). People with MS have patches of damage in the CNS. This damage, in the form of plaques or lesions, can result in partial or occasionally, total loss of bodily functions that are controlled by areas of the CNS.
The CNS is made up of the brain and the spinal cord and contains many neurons which perform numerous functions, such as transmission of information and control of bodily functions. Neurons comprise a cell body, dendrites which are responsible for receiving information from other neurons, and axons (or nerve fibres). The importance of the axons lies in their ability to allow very weak electrical signals to travel along them; in this way, information and instructions are passed from the CNS to the body.
When looked at with the naked eye, areas where the cell bodies and dendrites are clumped together in the tissues of the CNS look grey. For this reason, they are known as ‘grey matter’.
The ‘white matter’ includes those parts of the CNS where the axons are enclosed in myelin which is a fatty substance made up of cell membranes. This substance is wrapped many times around the axons and enables information and instructions (electrical signals or impulses) to be sent more quickly from the brain to the rest of the body, or from a particular part of the body back to the brain (Moffett D, Moffett S, Schauf C (Eds). Human Physiology, 2nd ed. Mosby-Year Book Inc; St Louis, Mo., USA, 1993).
Multiple sclerosis can run at least three clinical courses: (i) relapsing-remitting (RR) MS, which is most frequent (˜85%) and characterised by discrete attacks (exacerbations) and subsequent periods of clinical stability. In most relapsing MS patients, (ii) a secondary progressive (SP) phase ensues, with continuously increasing deficits. About 10-15% of MS patients develop steadily increasing neurological deficits from onset, (iii) the primary-progressive subtype (Nosworthy et al., N Engl J Med 2000; 343, 938-952).
Multiple sclerosis typically comprises two phases: an initial inflammatory phase followed by a neurodegenerative phase.
The brain and the nervous system are nourished by capillaries and are protected by the blood-brain barrier which is an envelope of tightly packed cells that permits only oxygen and nutrients passing over from the blood (Haslet C, Chivers E R, Boon N A et al (Eds). Davidson's Principles and Practice of Medicine, 19th ed. Churchill Livingstone; Edinburgh: 2002). Sometimes this barrier breaks down and other molecules, such as antibodies and even cells, can cross the barrier. T-cells are key members of the body's immune system and it is generally accepted that the inflammatory phase of MS is caused by abnormally functioning myelin-specific CD4+ T helper 1 (TH1) cells leaking out of the blood vessels and causing swelling and damage (inflammation) in the white matter (myelin) (Hafler, D. A. et al., Immunol Rev 2005; 204, 208-231; Sospedra, M. and Martin, R., Annu Rev Immunol 2005; 23, 683-747).
The T-cells also produce chemicals which attack and break down the myelin sheath of the axons. Both the myelin and the cells that produce myelin are attacked (Noseworthy J H et al., Multiple sclerosis. New Eng J Med 2000; 343: 938-952). This process is an example of an ‘autoimmune reaction’. When this ‘demyelination’ (i.e. damage to the myelin) happens, the passage of information and instructions through electrical signals that travel along the axons is inhibited. When the damage becomes significant, people with MS experience typical symptoms: poor muscle coordination, numbness or tingling, weakness and fatigue and other problems.
Once the inflammation phase of MS subsides, cells within the CNS begin to repair the damaged myelin. This process is called ‘remyelination,’ or restoration of the myelin. This cycle of damage and recovery occurs repeatedly in the myelin, often unnoticed, especially in the early stages of the disease. When, and to what extent, symptoms become apparent depends on the location, extent and severity of inflammation. If the inflammation occurs repeatedly in the same place, the repair processes may not be able to ‘keep up’, and permanent damage to the axons may occur which triggers the neurodegenerative phase (Steinman Nature Immunology 2, 762-764 (2001).
The signs and symptoms of MS are variable, but can include numbness, pain, pins and needles, muscle weakness or spasms, blurred vision, and fatigue, inter alia. For some people, MS episodes can be unpredictable and will include periods of relapse and remission. For others, the disease can be progressive.
MS is the commonest neurological disease of young adults, afflicting at least one million people between 17 and 65 years of age worldwide (Kantarci, O and Wingerchuk, D, Curr Opin Neurol 2006, 19:248-254.). The onset of MS will typically occur between the ages of 20 and 40 and generally affects twice as many women as men (Kantarci, O and Wingerchuk, D, Curr Opin Neurol 2006, 19:248-254.)
MS is a lifelong disease. Although no cure exists as yet, there are treatments that have been shown to reduce relapses—and some slow the progression of disability and are often called disease-modifying treatments, such as interferon beta (IFN-β), mitroxantrone and glatiramer acetate.
Another group of compounds, called corticosteroids, have also been used to control some of the symptoms of relapse in people with MS.
Thus, there is an ongoing need to find alternative and effective treatments for multiple sclerosis and other demyelinating diseases.